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Objectives. To investigate the distribution of radiolabelled interleukin-1 receptor antagonist (IL-1ra) in patients with rheumatoid arthritis (RA) and to assess whether this cytokine is suitable for scintigraphic visualization of synovitis.
Methods. In patients with active RA, scintigraphy was performed after a single i.v. dose of [¹²³I]IL-1ra. Clearance and organ distribution of radiolabelled IL-1ra were studied. To assess whether radiolabelled IL-1ra targets the synovial IL-1 receptors, the scintigraphic images obtained with IL-1ra were compared with those obtained by the use of a non-specific control agent. In addition, autoradiography was performed in mice with antigen-induced arthritis that were injected with either radiolabelled IL-1ra or a size-matched, non-receptor-binding protein.
Results. Radiolabelled IL-1ra allowed clear visualization of inflamed joints. Specificity in the detection of synovitis was high, whereas a number of painful and swollen joints were not visualized by scintigraphy. The procedure was well tolerated and [¹²³I]IL-1ra was rapidly cleared from the circulation (t<inf>1/2</inf>α 11 min, t<inf>1/2</inf>β 612 min) and excreted mainly in the urine. The definition of synovial contours by IL-1ra scintigraphy was not better than that observed with a non-specific agent. Although radiolabelled IL-1ra retained its affinity for IL-1 receptors, no binding to synovium was observed by autoradiography.
Conclusions. Radiolabelled IL-1ra allows the visualization of synovitis in patients with RA. However, neither the imaging nor the autoradiographic studies indicate that joint accumulation of radiolabelled IL-1ra is due to specific IL-1 receptor targeting. IL-1ra has proved its therapeutic value in RA, but with the dose schedule in this study it does not behave as a specific radiopharmaceutical that is suitable for scintigraphic detection of inflammation.

Radiolabelled interleukin-8 (IL-8) is a promising, agent for the imaging of infection and inflammation. Several experiments were performed to explore further the imaging potential of radiolabelled IL-8. IL-8 was radioiodinated via the Bolton-Hunter method. Rabbits with focal infection (Escherichia coli, Staphylococcus auresu) or sterile inflammation (zymosan) were injected intravenously with 18.5 MBq (0.5 mCi) of 123I-IL-8. In separate studies, rabbits were injected intravenously with 111In-granulocytes with or without 125-I-IL-8. Gamma camera images were obtained at 5 min, 1, 4 and 8 h post-injection (p.). Biodistribution was determined at 8 h p.i. In all models, the biodistribution of 123-I-IL-8 was characterized by rapid blood clearance and high uptake in infection and sterile inflammation. All foci could be clearly visualized within 4 h p.i. Ex vivoabscess-to-contralateral muscle ratios increased to 114.7 $$ 23.0 (E. coli), 52.3 $$ 24.5 (S. aureus) and 49.8 $$ 8.3 (zymosan) at 8 h p.i. In the circulation, most 123I-IL-8 was bound to erythrocytes. The abscess uptake of 125I-IL-8 reached high levels despite reduced migration of granulocytes towards the site of infection due to the anti-inflammatory activity of intravenously injected IL-8. IL-8 could be injected without induction of neutropenia at a dosage of 2 ng kg-1, In conclusion, the characteristics of radiolabelled IL-8 for imaging of infection and sterile inflammation are highly encouraging and warrant further optimization for clinical application.

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